The major aim is to determine the mechanisms of the biosynthesis of purine nucleotides and their derivatives in microorganisms. Auxotrophic mutants are used to unravel the essential steps, to obtain genetic alterations of the reactions, to determine the interplay of purine biosynthesis with that of vitamins such as thiamine and folate cofactors. Genetic control of the expression of the enzymes is studied by identifying multigenic units of functional control (operon) and determining the factors which control the expression of genes. Particular attention will be placed on the metabolic mechanisms which regulate these processes, the genetic devices which alter them, and mutational events which impair or modify their regulation. Special reactions are under consideration: 1) the multi-enzyme system involved in the formation of the first intermediate, phosphoribosylamine, 2) the IMP-cyclohydrolase-transformylase complex, 3) IMP dehydrogenase, 4) XMP aminase, 5) GMP reductase, and 6) purine phosphoribosyl-transferase. The role of cyclic AMP as a regulator of these processes is also under study.